FABH_MYCTU
ID FABH_MYCTU Reviewed; 335 AA.
AC P9WNG3; L0T424; O06399; P0A574;
DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot.
DT 16-APR-2014, sequence version 1.
DT 03-AUG-2022, entry version 42.
DE RecName: Full=3-oxoacyl-[acyl-carrier-protein] synthase 3 {ECO:0000255|HAMAP-Rule:MF_01815};
DE EC=2.3.1.180 {ECO:0000255|HAMAP-Rule:MF_01815};
DE AltName: Full=3-oxoacyl-[acyl-carrier-protein] synthase III {ECO:0000255|HAMAP-Rule:MF_01815};
DE AltName: Full=Beta-ketoacyl-ACP synthase III {ECO:0000255|HAMAP-Rule:MF_01815};
DE Short=KAS III {ECO:0000255|HAMAP-Rule:MF_01815};
DE AltName: Full=MtFabH {ECO:0000303|PubMed:10840036};
GN Name=fabH; OrderedLocusNames=Rv0533c; ORFNames=MTCY25D10.12c;
OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv).
OC Bacteria; Actinobacteria; Corynebacteriales; Mycobacteriaceae;
OC Mycobacterium; Mycobacterium tuberculosis complex.
OX NCBI_TaxID=83332;
RN [1]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=9634230; DOI=10.1038/31159;
RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., Harris D.E.,
RA Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, Tekaia F., Badcock K.,
RA Basham D., Brown D., Chillingworth T., Connor R., Davies R.M., Devlin K.,
RA Feltwell T., Gentles S., Hamlin N., Holroyd S., Hornsby T., Jagels K.,
RA Krogh A., McLean J., Moule S., Murphy L.D., Oliver S., Osborne J.,
RA Quail M.A., Rajandream M.A., Rogers J., Rutter S., Seeger K., Skelton S.,
RA Squares S., Squares R., Sulston J.E., Taylor K., Whitehead S.,
RA Barrell B.G.;
RT "Deciphering the biology of Mycobacterium tuberculosis from the complete
RT genome sequence.";
RL Nature 393:537-544(1998).
RN [2]
RP FUNCTION, SUBSTRATE SPECIFICITY, CATALYTIC ACTIVITY, ACTIVITY REGULATION,
RP AND PATHWAY.
RX PubMed=10840036; DOI=10.1074/jbc.m003241200;
RA Choi K.-H., Kremer L., Besra G.S., Rock C.O.;
RT "Identification and substrate specificity of beta -ketoacyl (acyl carrier
RT protein) synthase III (mtFabH) from Mycobacterium tuberculosis.";
RL J. Biol. Chem. 275:28201-28207(2000).
RN [3]
RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS].
RX PubMed=19099550; DOI=10.1186/1752-0509-2-109;
RA Raman K., Yeturu K., Chandra N.;
RT "targetTB: a target identification pipeline for Mycobacterium tuberculosis
RT through an interactome, reactome and genome-scale structural analysis.";
RL BMC Syst. Biol. 2:109-109(2008).
RN [4]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, CLEAVAGE OF INITIATOR
RP METHIONINE [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY
RP [LARGE SCALE ANALYSIS].
RC STRAIN=ATCC 25618 / H37Rv;
RX PubMed=21969609; DOI=10.1074/mcp.m111.011627;
RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., Yadav A.K.,
RA Shrivastava P., Marimuthu A., Anand S., Sundaram H., Kingsbury R.,
RA Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., Katoch K., Katoch V.M.,
RA Kumar P., Chaerkady R., Ramachandran S., Dash D., Pandey A.;
RT "Proteogenomic analysis of Mycobacterium tuberculosis by high resolution
RT mass spectrometry.";
RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011).
RN [5]
RP X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS), FUNCTION, CATALYTIC ACTIVITY,
RP SUBUNIT, AND ACTIVE SITE.
RX PubMed=11278743; DOI=10.1074/jbc.m010762200;
RA Scarsdale J.N., Kazanina G., He X., Reynolds K.A., Wright H.T.;
RT "Crystal structure of the Mycobacterium tuberculosis beta-ketoacyl-acyl
RT carrier protein synthase III.";
RL J. Biol. Chem. 276:20516-20522(2001).
RN [6]
RP X-RAY CRYSTALLOGRAPHY (2.7 ANGSTROMS).
RA Sacchettini J.C., Sridharan S.;
RT "X-ray crystal structure of Mycobacterium tuberculosis beta-ketoacyl-acyl
RT carrier protein synthase III (MtFabH).";
RL Submitted (JUN-2002) to the PDB data bank.
CC -!- FUNCTION: Catalyzes the condensation reaction of fatty acid synthesis
CC by the addition to an acyl acceptor of two carbons from malonyl-ACP.
CC Catalyzes the first condensation reaction which initiates fatty acid
CC synthesis and may therefore play a role in governing the total rate of
CC fatty acid production. Possesses both acetoacetyl-ACP synthase and
CC acetyl transacylase activities. Possesses a clear preference for long-
CC chain acyl-CoA substrates rather than acyl-ACP primers, and shows only
CC weak activity with acetyl-CoA. Its substrate specificity determines the
CC biosynthesis of mycolic acid fatty acid chain, which is characteristic
CC of mycobacterial cell wall. {ECO:0000269|PubMed:10840036,
CC ECO:0000269|PubMed:11278743}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=acetyl-CoA + H(+) + malonyl-[ACP] = 3-oxobutanoyl-[ACP] + CO2
CC + CoA; Xref=Rhea:RHEA:12080, Rhea:RHEA-COMP:9623, Rhea:RHEA-
CC COMP:9625, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57288, ChEBI:CHEBI:78449, ChEBI:CHEBI:78450;
CC EC=2.3.1.180; Evidence={ECO:0000255|HAMAP-Rule:MF_01815};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexanoyl-CoA + malonyl-[ACP] = 3-oxooctanoyl-[ACP] +
CC CO2 + CoA; Xref=Rhea:RHEA:42256, Rhea:RHEA-COMP:9623, Rhea:RHEA-
CC COMP:9633, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:62620, ChEBI:CHEBI:78449, ChEBI:CHEBI:78460;
CC Evidence={ECO:0000269|PubMed:11278743};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42257;
CC Evidence={ECO:0000269|PubMed:11278743};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-[ACP] + octanoyl-CoA = 3-oxodecanoyl-[ACP] +
CC CO2 + CoA; Xref=Rhea:RHEA:42264, Rhea:RHEA-COMP:9623, Rhea:RHEA-
CC COMP:9637, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:57386, ChEBI:CHEBI:78449, ChEBI:CHEBI:78464;
CC Evidence={ECO:0000269|PubMed:10840036, ECO:0000269|PubMed:11278743};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:42265;
CC Evidence={ECO:0000269|PubMed:10840036, ECO:0000269|PubMed:11278743};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=decanoyl-CoA + H(+) + malonyl-[ACP] = 3-oxododecanoyl-[ACP] +
CC CO2 + CoA; Xref=Rhea:RHEA:43652, Rhea:RHEA-COMP:9623, Rhea:RHEA-
CC COMP:9641, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, ChEBI:CHEBI:57287,
CC ChEBI:CHEBI:61430, ChEBI:CHEBI:78449, ChEBI:CHEBI:78469;
CC Evidence={ECO:0000269|PubMed:10840036};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43653;
CC Evidence={ECO:0000269|PubMed:10840036};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=dodecanoyl-CoA + H(+) + malonyl-[ACP] = 3-oxotetradecanoyl-
CC [ACP] + CO2 + CoA; Xref=Rhea:RHEA:43640, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9645, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57375, ChEBI:CHEBI:78449,
CC ChEBI:CHEBI:78473; Evidence={ECO:0000269|PubMed:10840036,
CC ECO:0000269|PubMed:11278743};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43641;
CC Evidence={ECO:0000269|PubMed:10840036, ECO:0000269|PubMed:11278743};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + malonyl-[ACP] + tetradecanoyl-CoA = 3-oxohexadecanoyl-
CC [ACP] + CO2 + CoA; Xref=Rhea:RHEA:43644, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9649, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57385, ChEBI:CHEBI:78449,
CC ChEBI:CHEBI:78478; Evidence={ECO:0000269|PubMed:10840036,
CC ECO:0000269|PubMed:11278743};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43645;
CC Evidence={ECO:0000269|PubMed:10840036, ECO:0000269|PubMed:11278743};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=H(+) + hexadecanoyl-CoA + malonyl-[ACP] = 3-oxooctadecanoyl-
CC [ACP] + CO2 + CoA; Xref=Rhea:RHEA:43648, Rhea:RHEA-COMP:9623,
CC Rhea:RHEA-COMP:9653, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526,
CC ChEBI:CHEBI:57287, ChEBI:CHEBI:57379, ChEBI:CHEBI:78449,
CC ChEBI:CHEBI:78487; Evidence={ECO:0000269|PubMed:10840036,
CC ECO:0000269|PubMed:11278743};
CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:43649;
CC Evidence={ECO:0000269|PubMed:10840036, ECO:0000269|PubMed:11278743};
CC -!- ACTIVITY REGULATION: Sensitive to thiolactomycin and resistant to
CC cerulenin in vitro. {ECO:0000269|PubMed:10840036}.
CC -!- PATHWAY: Lipid metabolism; fatty acid biosynthesis. {ECO:0000255|HAMAP-
CC Rule:MF_01815}.
CC -!- PATHWAY: Lipid metabolism; mycolic acid biosynthesis.
CC {ECO:0000305|PubMed:10840036}.
CC -!- SUBUNIT: Homodimer. {ECO:0000255|HAMAP-Rule:MF_01815,
CC ECO:0000269|PubMed:11278743}.
CC -!- SUBCELLULAR LOCATION: Cytoplasm {ECO:0000255|HAMAP-Rule:MF_01815}.
CC -!- DOMAIN: The last Arg residue of the ACP-binding site is essential for
CC the weak association between ACP/AcpP and FabH. {ECO:0000255|HAMAP-
CC Rule:MF_01815}.
CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target.
CC {ECO:0000269|PubMed:19099550}.
CC -!- SIMILARITY: Belongs to the thiolase-like superfamily. FabH family.
CC {ECO:0000255|HAMAP-Rule:MF_01815, ECO:0000305}.
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DR EMBL; AL123456; CCP43271.1; -; Genomic_DNA.
DR PIR; H70545; H70545.
DR RefSeq; NP_215047.1; NC_000962.3.
DR RefSeq; WP_003402861.1; NZ_NVQJ01000036.1.
DR PDB; 1HZP; X-ray; 2.10 A; A/B=1-335.
DR PDB; 1M1M; X-ray; 2.70 A; A/B=1-335.
DR PDB; 1U6E; X-ray; 1.85 A; A/B=1-335.
DR PDB; 1U6S; X-ray; 2.30 A; A/B=1-335.
DR PDB; 2AHB; X-ray; 2.00 A; A/B=1-335.
DR PDB; 2AJ9; X-ray; 2.50 A; A/B=1-335.
DR PDB; 2QNX; X-ray; 2.70 A; A/B=1-335.
DR PDB; 2QNY; X-ray; 2.15 A; A/B=1-335.
DR PDB; 2QNZ; X-ray; 2.30 A; A/B=1-335.
DR PDB; 2QO0; X-ray; 1.85 A; A/B=1-335.
DR PDB; 2QO1; X-ray; 2.60 A; A/B=1-335.
DR PDB; 2QX1; X-ray; 2.60 A; A/B=1-335.
DR PDBsum; 1HZP; -.
DR PDBsum; 1M1M; -.
DR PDBsum; 1U6E; -.
DR PDBsum; 1U6S; -.
DR PDBsum; 2AHB; -.
DR PDBsum; 2AJ9; -.
DR PDBsum; 2QNX; -.
DR PDBsum; 2QNY; -.
DR PDBsum; 2QNZ; -.
DR PDBsum; 2QO0; -.
DR PDBsum; 2QO1; -.
DR PDBsum; 2QX1; -.
DR AlphaFoldDB; P9WNG3; -.
DR SMR; P9WNG3; -.
DR STRING; 83332.Rv0533c; -.
DR BindingDB; P9WNG3; -.
DR ChEMBL; CHEMBL3640; -.
DR DrugBank; DB08712; 11-[(MERCAPTOCARBONYL)OXY]UNDECANOIC ACID.
DR DrugBank; DB08171; 11-MERCAPTOUNDECANOIC ACID.
DR DrugBank; DB07611; DECANE-1-THIOL.
DR DrugBank; DB07650; Decyl formate.
DR DrugBank; DB03264; Dodecyl-Coa.
DR DrugBank; DB03017; Lauric acid.
DR DrugBank; DB08684; O-Decyl Hydrogen Thiocarbonate.
DR SwissLipids; SLP:000000966; -.
DR iPTMnet; P9WNG3; -.
DR PaxDb; P9WNG3; -.
DR DNASU; 887381; -.
DR GeneID; 45424497; -.
DR GeneID; 887381; -.
DR KEGG; mtu:Rv0533c; -.
DR TubercuList; Rv0533c; -.
DR eggNOG; COG0332; Bacteria.
DR OMA; WGSEGDK; -.
DR PhylomeDB; P9WNG3; -.
DR BioCyc; MetaCyc:G185E-4666-MON; -.
DR BRENDA; 2.3.1.180; 3445.
DR BRENDA; 2.3.1.301; 3445.
DR UniPathway; UPA00094; -.
DR UniPathway; UPA00915; -.
DR PRO; PR:P9WNG3; -.
DR Proteomes; UP000001584; Chromosome.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-SubCell.
DR GO; GO:0004315; F:3-oxoacyl-[acyl-carrier-protein] synthase activity; IDA:MTBBASE.
DR GO; GO:0033818; F:beta-ketoacyl-acyl-carrier-protein synthase III activity; IDA:MTBBASE.
DR GO; GO:0061990; F:beta-ketodecanoyl-[acyl-carrier-protein] synthase activity; IEA:RHEA.
DR GO; GO:0000062; F:fatty-acyl-CoA binding; IDA:MTBBASE.
DR GO; GO:0006633; P:fatty acid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0030497; P:fatty acid elongation; IDA:MTBBASE.
DR GO; GO:0008610; P:lipid biosynthetic process; IDA:MTBBASE.
DR GO; GO:0035336; P:long-chain fatty-acyl-CoA metabolic process; IDA:MTBBASE.
DR Gene3D; 3.40.47.10; -; 2.
DR HAMAP; MF_01815; FabH; 1.
DR InterPro; IPR013751; ACP_syn_III.
DR InterPro; IPR013747; ACP_syn_III_C.
DR InterPro; IPR004655; FabH_synth.
DR InterPro; IPR016039; Thiolase-like.
DR Pfam; PF08545; ACP_syn_III; 1.
DR Pfam; PF08541; ACP_syn_III_C; 1.
DR SUPFAM; SSF53901; SSF53901; 1.
DR TIGRFAMs; TIGR00747; fabH; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Acyltransferase; Cytoplasm;
KW Fatty acid biosynthesis; Fatty acid metabolism; Lipid biosynthesis;
KW Lipid metabolism; Multifunctional enzyme; Reference proteome; Transferase.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0007744|PubMed:21969609"
FT CHAIN 2..335
FT /note="3-oxoacyl-[acyl-carrier-protein] synthase 3"
FT /id="PRO_0000110443"
FT REGION 259..263
FT /note="ACP-binding"
FT /evidence="ECO:0000255|HAMAP-Rule:MF_01815"
FT ACT_SITE 122
FT /evidence="ECO:0000305|PubMed:11278743"
FT ACT_SITE 258
FT /evidence="ECO:0000305|PubMed:11278743"
FT ACT_SITE 289
FT /evidence="ECO:0000305|PubMed:11278743"
FT MOD_RES 2
FT /note="N-acetylthreonine"
FT /evidence="ECO:0007744|PubMed:21969609"
FT STRAND 13..21
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 24..28
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 29..32
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 35..37
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 40..47
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 50..54
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 61..76
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 80..82
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 85..89
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 96..98
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 100..108
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 113..119
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 121..123
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 124..137
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 142..151
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 153..155
FT /evidence="ECO:0007829|PDB:1U6E"
FT TURN 161..166
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 169..178
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 188..191
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 193..198
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 199..203
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 205..209
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 223..245
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 249..251
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 254..257
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 262..272
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 284..287
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 291..293
FT /evidence="ECO:0007829|PDB:1U6E"
FT HELIX 294..304
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 306..308
FT /evidence="ECO:0007829|PDB:2AJ9"
FT STRAND 313..320
FT /evidence="ECO:0007829|PDB:1U6E"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:1U6E"
FT STRAND 324..331
FT /evidence="ECO:0007829|PDB:1U6E"
SQ SEQUENCE 335 AA; 34873 MW; 6573BE1FAE5BCFB6 CRC64;
MTEIATTSGA RSVGLLSVGA YRPERVVTND EICQHIDSSD EWIYTRTGIK TRRFAADDES
AASMATEACR RALSNAGLSA ADIDGVIVTT NTHFLQTPPA APMVAASLGA KGILGFDLSA
GCAGFGYALG AAADMIRGGG AATMLVVGTE KLSPTIDMYD RGNCFIFADG AAAVVVGETP
FQGIGPTVAG SDGEQADAIR QDIDWITFAQ NPSGPRPFVR LEGPAVFRWA AFKMGDVGRR
AMDAAGVRPD QIDVFVPHQA NSRINELLVK NLQLRPDAVV ANDIEHTGNT SAASIPLAMA
ELLTTGAAKP GDLALLIGYG AGLSYAAQVV RMPKG
